Thyroglobulin will be reduced and alkylated under previously established conditions, and cleaved with cyanogen bromide. Different preparative techniques will be used including molecular sieving filtration methods, ionic exchange chromatography, hydrophobe chromatography, etc., to purify iodinated peptides. The iodopeptides will be characterized by analytical methods. Antisera will be obtained against thyroglobulin fragments and their reaction with intact and digested thyroglobulin studied by immunochemical methods including affinity chromatography. The interaction of the fragments with thyroid peroxidase-iodination system will also be studied. Sequencing of the iodopeptides will be done in the future in order to find out the possible relationship between thyroglobulin structure and function, i.e. biosynthesis of thyroid hormone. In parallel, studies will be conducted on human thyroid tissues regarding their proteosynthetic activity as measured by 14C-amino acid incorporation into thyroid protein. The component corresponding to thyroglobulin will be differentiated by immunochemical methods. We have previously demonstrated the inhibitory effect of iodide on thyroid protein synthesis in rats. This will be applied to the study of different human pathologic tissues. Studies will be also continued on the ultrastructure of thyroid tumors.